Factors

We need to know every factor which determines lifespan.

Lifespan factors often but not always originate from defined genetic elements. They are not just genes, by definition they can be anything for which a Classifications schema can be build for that is related to the regulation of lifespan, such entities may include Single-Nucleotide Polymorphism, transcript variants, proteins and their complexes, compounds (i.e. small molecules like metabolites and drugs), etc. A factor should be based on a defined molecular entity or genomic position and been classified. It shall be highly flexible and scalable Concept.

While individual lifespan factors within each species or precise defined molecular entities will be captured within the Lifespan App, Data Entries of the Data App may summarize for instance the relevance of each factor class (e.g. homologous group; chemical derivate of related structure and properties, etc.) as well as draw overall conclusions.
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Animals engineered to overexpress bovine MSRA in the nervous system have an extended median lifespan by up to 70% (relative to parental control), increased resistance to oxidative stress, and delayed the onset of senescence-induced decline in activity levels and reproductive capacity [11867705].

In budding yeast treatment with rapamcyin increases mean and maximum replicative lifespan by 19 and 16% Rapamycin fails to extend the lifespan of sir2 mutants or NAM treated wild-type cells [20947565]. Rapamcyin treatment increases mean chronological lifespan by by approximately by 80% in BY4742 [22790951]. Rapamycin extends chronological lifespan proportional with increasing concentrations from 100 pg/mL to 1 ng/mL [16418483].
Treatment with rapamcyin in nemaotdes increases mean, median, 75th %ile and maximum lifespan by 19-29, 17-29, 24-32 an 19%, respectively on OP50. On HT115 rapamycyin extends mean, median and 75th %ile of lifespan by 8-36, 4-46 and 12-44%, respectively. Rapamycin robustly increases lifespan in two daf-16 mutants (mgDf47 and mu86) with or without FUdR and with growth on either the standard strain OP50 or the feeding RNAi strain HT115 [22560223].
Treatment of Drosophila imago with rapamycin induces increases of median (by 5-6%) lifespan (p < 0.01) in males and females, respectively and increase of maximum lifespan (by 33%) in females (p < 0.01) [22661237]. Rapamcyin increases mouse lifespan even when administrated late in life [19587680].
Low dose of rapamycin (5 microM) slightly increase the median and maximum lifespan in fruit fly [20017609].
Rapamcyin increases mouse lifespan and healthspan even when administrated late in life (20 months) [19587680].
Rapamycin enhances learning and memory in young mice and improves these faculties in old mice thereby negating the normal decline in these functions with age. Rapamycin boost levels of neurotransmitters associated with neural plasticity. Rapamycin also lowered anxiety and depressive-like behaviour at all ages from 4, 12 and 28 months. "Happy, feel-good" neurotransmitters such as serotonin, dopamine and norepinephrine are all significantly augmented in the midbrains of rapamycin treated mice [http://denigma.de/url/37].
Treatment with rapamycin increased lifespan and suppresses spontanous tumorgenesis in inbred female mice [22107964].

Curcumin increases lifespan in *C. elegans* and is associated with reduced ROS and lipofuscin during aging. Curcumin lifespan extension is attributed to its antioxidative properties. Lifespan extension had effects on body size and pharyngeal pumping rate but not on reproduction. Lifespan-extension by curcumin is abolished in osr-1, sek-1, mek-1, skn-1, unc-43, sir-2.1 and age-1 mutants, whereas curcumin treatment prolongs lifespan of mev-1 and daf-16 mutants [21855561]. *C. elegans* feed low concentration of curcumin have a decreased lipofuscin levels and enhanced the resistance to heat stress and increased mean lifespan by 39% and a maximum lifespan extended by 21.4% [23325575]. In fruit fly that survive an average of 64 days, an increase of mean lifespan to 80 days occurs in flies, with females of one strain and males of another strain experiencing an extension in lifespan. The lifespan response to curcimun exhibits variation in male and female, although the compound extends lifespan in both genders [23325575].
In fruit fly, 0.5 an 1.0 mg/g curcumin in the diet increases mean lifespan by 6.2 and 25% in females and by 15.5 and 12.6 in males, respectively. Lifespan extension by curcumin was associated with the increased superoxide dismutase (SOD) activity, upregulation of Ms-SOD and CuZn-SOD genes, and the downregulation of *dInR*, *ATTD*, *Def*, *CecB* and, *DptB* genes as well as reduction of lipofuscin, malondialdehyde and lipid peroxidation [22653297; 23325575]. Curcumin prolongs life and enhances activity of fruit fly Alzheimer diseased flies [22348084].

Treatment of C. elegans with 65 microgram/mL Procyanidins from apple extends the lifespan of N2 and FEM-1 by 12.1 to 8.4%, respectively and does not modify grwoth, food intake of fecundity. Procyanidin treatment has no effect on mev-1 or sir-2.1 mutants [20717869].

Apple polyphenols mainly consists of procyanidins, which are composed of (-)-epicatechins and (+)-catechins. Treatment of C. elegans with 100 microgram/mL apple polyphenol increases mean lifespan of wild-type N2 and FEM-1 by 12.0 and 5.3%, respectively [20717869].
In fruit flies, supplemention of the diet with apple polyphenol significantly extends mean lifespan by 10% and is accompanied by up-regulation of SOD1, SOD2 and CAT as well as downregulation of MTH in aged animals [21319854].

Overexpression of SIR2RP1 results in a significant increase in survival of the vertebrate stage under normla axenic culture conditions, but has no effect on survival of the insect stage of the parasite. SIR2RP1 is mainly localized within the cytoplasm [12383511].

In budding yeast, the hypersensitivity to oxygene and significantly decreased replicative lifespan of SOD1 deletion can be ameliorated by exogenous ascorbate. If acorbate's negative effects of auto-oxidation are prevented by exchange of medium, ascorbate prolongs mean and maximum replicative lifespan in the atmosphere of air and pure oxygene [15621721].

Treatment with 0.5 and 2% DMSO increases lifespan by 24.4 and 23.0%, respectively. 0.5% DMSO does not affect progeny number or lifespan under thermal stress. Treatment with 0.5% DMSO enhances the mRNA levels of hsp-16.2, hsp-70, lys-7, old-1, and sod-5 by 2.5, 2.9, 1.3, 2.3, and 4.5-fold, respectively, as well as the protein level of lys-7 by 1.5-fold. Lifespan extension confered by DMSO depends on sir-2.1 and daf-16 but not on eat-2 or hsf-1 [20828537].

High jugelone concentrations led to premature death. Low juglone concentrations are tolerated well and cause a prolongation of lifespan that is associated with increased expression of small heat-shock protein HSP-16.2, enhanced glutathione levels, and nuclear translocation of DAF-16. Silencing or deletion of daf-16 prevents jugelone-induced adaptations. RNA-interference for SIR-2.1 has the same effects as daf-16 deletion but does not affect nuclear accumulation of DAF-16. DAF-16- and SIR-2.1-dependent alterations in gene expression after challenge with reactive oxygene species lead to lifespan extension [19597959].

Deletion of the WRKY6 promoter results in defects in root and leaf cell senescence [11722756].
WRKY6 is a transcription factor involved in controlling processes related to senescence and pathogen defence [11722756] and is a positive regulator of PR1 expression [12000796]. WRKY6 is strongly expressed during senescence [11722756].

In budding yeast addition of 0.5 mg/ml D-glucosamine to the growth media suppresses the short replicative lifespan and temperature sensitive growth of mpt5 mutant, but fails to extend the lifespan of wild-type cells [11805047].